2-[(2S,5S,9S)-5-benzyl-9-[3-(diaminomethylideneamino)propyl]-3,8,11,13-tetraoxo-1,4,7,10-tetrazacyclotridec-2-yl]acetic acid | 1202508-62-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: 2-[(2S,5S,9S)-5-benzyl-9-[3-(diaminomethylideneamino)propyl]-3,8,11,13-tetraoxo-1,4,7,10-tetrazacyclotridec-2-yl]acetic acid
• CAS: 1202508-62-0
• 化学式: C₂₂H₃₁N₇O₆
• 分子量: 489.531
• InChiKey: JBCUWZUACLSOTF-JYJNAYRXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  218
• 氢给体数：
  7
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  tert-butyl 2-[(2S,5S,9S)-9-[3-[[amino-[(4-methoxy-2,3,6-trimethylphenyl)sulfonylamino]methylidene]amino]propyl]-5-benzyl-3,8,11,13-tetraoxo-1,4,7,10-tetrazacyclotridec-2-yl]acetate 在 乙硫醚 、 苯硫酚 、 三氟乙酸 、 苯酚 作用下， 以 水 为溶剂， 反应 0.5h， 以76%的产率得到2-[(2S,5S,9S)-5-benzyl-9-[3-(diaminomethylideneamino)propyl]-3,8,11,13-tetraoxo-1,4,7,10-tetrazacyclotridec-2-yl]acetic acid
  参考文献：
  名称：

  Antiangiogenic Effect of Dual/Selective α₅β₁/α_vβ₃ Integrin Antagonists Designed on Partially Modified Retro-Inverso Cyclotetrapeptide Mimetics

  摘要：

  Recent evidence highlighted the role of alpha(5)beta(1) integrin in angiogenesis and In regulating alpha(v)beta(3) integrin function. As a consequence, selective alpha(5)beta(1) integrin inhibitors or dual alpha(5)beta(1)/alpha(v)beta(3) integrin inhibitors are considered promising candidates for the development of cancer therapeutic agents. In this paper, we describe the synthesis and pharmacological characterization of a minilibrary of cyclotetrapeptide mimetics containing a PMRI Arg-Gly-Asp sequence. In particular, c[(R)-beta Phe psi(NHCO)Asp psi-(NHCO)Gly-Arg] (3) displayed a good activity in inhibiting the alpha(v)beta(3) integrin-mediated cell adhesion of fibronectin or vitronectin, its well as the adhesion of fibronectin to the alpha(5)beta(1) integrin. Interestingly, the diastereomeric compound c[(S)- beta Phe psi(NHCO)Asp psi(NHCO)Gly-Arg] (2) maintained a good efficacy in inhibiting alpha(5)beta(1) integrin while gaining a certain selectivity over alpha(v)beta(3) integrin. These two integrin antagonists significantly inhibited bFGF-induced human endothelial cell tube formation at submicromolar concentrations. Conformational analysis and Molecular Docking calculations Suggest that the different alpha(5)beta(1) versus alpha(v)beta(3) selectivity of 2 and 3 can be rationalized on the basis of the alternative display of the aromatic side chain adjacent to Asp.

  DOI：

  10.1021/jm9013532